Structure–Activity Relationship of Azaindole-Based Glucokinase Activators

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• 作者：Attila Paczal ; Balázs Bálint ; Csaba Wéber ; Zoltán B. Szabó ; Levente Ondi ; Isabelle Theret ; Frédéric De Ceuninck ; Catherine Bernard ; Alain Ktorza ; Francoise Perron-Sierra ; András Kotschy
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：January 28, 2016
• 年：2016
• 卷：59
• 期：2
• 页码：687-706
• 全文大小：723K
• ISSN：1520-4804

文摘

7-Azaindole has been identified as a novel bidentate anchor point for allosteric glucokinase activators. A systematic investigation around three principal parts of the new small molecule glucokinase activators led to a robust SAR in agreement with structural data that also helped to assess the conformational flexibility of the allosteric activation site. The increase in glucose uptake resulting from glucokinase activation in hepatocytes in vitro translated into the efficient lowering of glucose levels in vivo with the best compounds.